BCMA-targeted immunotherapy for multiple myeloma
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(2020) 13:125
REVIEW
Open Access
BCMA-targeted immunotherapy for multiple myeloma Bo Yu1, Tianbo Jiang2 and Delong Liu2*
Abstract B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development. Keywords: B cell maturation antigen, BCMA, Belantamab mafodotin, CAR-T, Antibody-drug conjugate, Bispecific T cell engager
Introduction Recent advances in novel therapeutics such as proteasome inhibitors (PI) and immunomodulatory drugs (IMiD) have significantly improved the treatment outcomes in patients with multiple myeloma (MM) [1–8]. However, most MM patients eventually relapse due to the development of drug resistance [9]. In addition, many of the current popular target antigens, such as CD38 and SLAMF7 (also known as CS1 or CD319), are also found in other normal tissues, thus leading to unwanted off-tumor toxicities [10, 11]. Therefore, novel treatment strategies are urgently needed, especially in high-risk relapsed/refractory (R/R) MM [12–15]. B cell maturation antigen (BCMA) or CD269, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF-17), is restrictively expressed in both normal and malignant plasma cells (PC) at high levels, which makes it an ideal target antigen for novel MM therapies [16, 17]. * Correspondence: [email protected] 2 Department of Medicine, New York Medical College and Westchester Medical Center, Valhalla, NY, USA Full list of author information is available at the end of the article
B cell maturation antigen (BCMA) BCMA is encoded by a 2.92-kb TNFRSF17 gene located on the short arm of chromosome 16 (16p13.13) and composed of 3 exons separated by 2 introns (Fig. 1). BCMA is a 184 amino acid and 20.2-kDa type III transmembrane glycoprotein, with the extracellular N terminus containing a conserved motif of 6 cysteines [18–21]. BCMA was found to be a member of tumor necrosis factor (TNF) receptor (TNFR) superfamily [22]. There are four natural splice variants of human BCMA that present with different receptor binding affinities, membrane-anchoring ability, and intracellular domain signaling [19, 23]. BCMA, along with the other two functionally related TNFR superfamily members, B cell activating factor (BAFF; also called BLyS) receptor (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), coordinates to regulate B cell proliferation maturation and survival, as well as differentiation into plasma cells (PCs)
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